Abstract
ObjectiveTo investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD).MethodsWe classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental State Examination score 28 ± 2) from the Amsterdam Dementia Cohort and Subjective Cognitive Impairment Cohort (SCIENCe) project according to the ATN model, as determined by amyloid PET or CSF β-amyloid (A), CSF p-tau (T), and MRI-based medial temporal lobe atrophy (N). All underwent extensive neuropsychological assessment. For 342 participants, follow-up was available (3 ± 2 years). As a control population, we included 124 participants without SCD.ResultsFifty-six (n = 385) participants had normal Alzheimer disease (AD) biomarkers (A-T-N-), 27% (n = 186) had non-AD pathologic change (A-T-N+, A-T+N-, A-T+N+), 18% (n = 122) fell within the Alzheimer continuum (A+T-N-, A+T-N+, A+T+N-, A+T+N+). ATN profiles were unevenly distributed, with A-T+N+, A+T-N+, and A+T+N+ containing very few participants. Cox regression showed that compared to A-T-N-, participants in A+ profiles had a higher risk of dementia with a dose-response pattern for number of biomarkers affected. Linear mixed models showed participants in A+ profiles showed a steeper decline on tests addressing memory, attention, language, and executive functions. In the control group, there was no association between ATN and cognition.ConclusionsAmong individuals presenting with SCD at a memory clinic, those with a biomarker profile A-T+N+, A+T-N-, A+T+N-, and A+T+N+ were at increased risk of dementia, and showed steeper cognitive decline compared to A-T-N- individuals. These results suggest a future where biomarker results could be used for individualized risk profiling in cognitively normal individuals presenting at a memory clinic.
Original language | English |
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Pages (from-to) | 46-58 |
Number of pages | 13 |
Journal | Neurology |
Volume | 95 |
Issue number | 1 |
Early online date | 10 Jun 2020 |
DOIs | |
Publication status | Published - 7 Jul 2020 |
Funding
The Article Processing Charge was funded by the authors. The Alzheimer Center Amsterdam is supported by Alzheimer Nederland and Stichting VUMC funds. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The clinical database structure was developed with funding from Stichting Dioraphte. The SCIENCe project is supported by a research grant from Gieskes-Strijbis fonds. W.M.v.d.F. holds the Pas-man chair. W.M.v.d.F. and P.J.V. received funding in the context of Deltaplan Dementie from ZonMW Memorabel (Netherlands Consortium of Dementia Cohorts [NCDC] project 73305095005) and Alzheimer Nederland. PET scans were funded by research grants from AVID and Piramal Neuroimaging. F.B. is supported by the University College London Hospitals NHS Foundation Trust Biomedical Research Center.
Funders | Funder number |
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NCDC | |
Netherlands Organization of Scientific Research | |
Piramal Neuroimaging | |
Boehringer Ingelheim | |
EU Joint Programme – Neurodegenerative Disease Research | |
Avid Radiopharmaceuticals | |
Takeda Canada | |
ZonMw | 73305095005 |
ZonMw | |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
University College London Hospitals NHS Foundation Trust |